title: Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism.
abstract: Serum insulin-like growth factor (IGF) -1 is secreted mainly by the liver and circulates bound to IGF-binding proteins (IGFBPs), either as binary complexes or ternary complexes with IGFBP-3 or IGFBP-5 and an acid-labile subunit (ALS). The purpose of this study was to genetically dissect the role of IGF-1 circulatory complexes in somatic growth, skeletal integrity, and metabolism. Phenotypic comparisons of controls and four mouse lines with genetic IGF-1 deficits-liver-specific IGF-1 deficiency (LID), ALS knockout (ALSKO), IGFBP-3 (BP3) knockout, and a triply deficient LID/ALSKO/BP3 line-produced several novel findings. 1) All deficient strains had decreased serum IGF-1 levels, but this neither predicted growth potential or skeletal integrity nor defined growth hormone secretion or metabolic abnormalities. 2) IGF-1 deficiency affected development of both cortical and trabecular bone differently, effects apparently dependent on the presence of different circulating IGF-1 complexes. 3) IGFBP-3 deficiency resulted in increased linear growth. In summary, each IGF-1 complex constituent appears to play a distinct role in determining skeletal phenotype, with different effects on cortical and trabecular bone compartments.
authors.affiliation: Endocrinology/Diabetes and Bone Disease, The Mt. Sinai School of Medicine, One Gustave L Levy Place, Box 1055, New York, NY 10029-6574, USA. shoshana.yakar@mssm.edu
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: Mary L
authors.initials: ML
authors.lastname: Bouxsein
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Wilson
authors.initials: W
authors.lastname: Mejia
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wu
authors.forename: Kelly
authors.initials: K
authors.lastname: Emerton
authors.forename: Valerie
authors.initials: V
authors.lastname: Williams
authors.forename: Karl
authors.initials: K
authors.lastname: Jepsen
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Schaffler
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Majeska
authors.forename: Oksana
authors.initials: O
authors.lastname: Gavrilova
authors.forename: Mariana
authors.initials: M
authors.lastname: Gutierrez
authors.forename: David
authors.initials: D
authors.lastname: Hwang
authors.forename: Patricia
authors.initials: P
authors.lastname: Pennisi
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Yves
authors.initials: Y
authors.lastname: Boisclair
authors.forename: John
authors.initials: J
authors.lastname: Pintar
authors.forename: Héctor
authors.initials: H
authors.lastname: Jasper
authors.forename: Horacio
authors.initials: H
authors.lastname: Domene
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.forename: David
authors.initials: D
authors.lastname: Clemmons
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000818:Animals; D001823:Body Composition; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000502:physiology; D050260:Carbohydrate Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D015430:Weight Gain
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I